Brush prodrugs and uses thereof

A macromonomer of Formula (I):

• or a salt thereof, wherein:
• each instance of RA is independently hydrogen, halogen, or substituted or unsubstituted, C1-6 alkyl;
• a is an integer from 1 to 20, inclusive;
• each instance of —Y—Z— is
• each instance of M is independently hydrogen or a pharmaceutical agent;
• each instance of m is independently an integer from 1 to 10, inclusive;
• each instance of L is independently substituted or unsubstituted, C1-200 alkylene, substituted or unsubstituted, C2-200 alkenylene, substituted or unsubstituted, C2-200 alkynylene, substituted or unsubstituted, C2-200 heteroalkylene, substituted or unsubstituted, C2-200 heteroalkenylene, or substituted or unsubstituted, C2-200 heteroalkynylene, wherein:
• optionally one or more carbons in each instance of the substituted or unsubstituted, C1-200 alkylene, substituted or unsubstituted, C2-200 alkenylene, substituted or unsubstituted, C2-200 alkynylene, substituted or unsubstituted, C2-200 heteroalkylene, substituted or unsubstituted, C2-200 heteroalkenylene, and substituted or unsubstituted, C2-200 heteroalkynylene are independently replaced with substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• and
• optionally one or more heteroatoms in each instance of the substituted or unsubstituted, C2-200 heteroalkylene, substituted or unsubstituted, C2-200 heteroalkenylene, and substituted or unsubstituted, C2-200 heteroalkynylene are independently replaced with substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• each instance of W is independently a single bond, —O—, —S—, or —NRE—;
• each instance of RE is independently hydrogen, substituted or unsubstituted, C1-6 alkyl, or a nitrogen protecting group;
• each instance of W′ is independently —O—, —S—, or —NRJ—;
• each instance of R′ is independently hydrogen, substituted or unsubstituted, C1-6 alkyl, or a nitrogen protecting group;
• each instance of RK and RL is independently hydrogen, halogen, substituted or unsubstituted, C1-6 alkyl, substituted or unsubstituted, C2-6 alkenyl, substituted or unsubstituted, C2-6 alkynyl, substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl, substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl, substituted or unsubstituted phenyl, substituted or unsubstituted, 5- or 6-membered, monocyclic heteroaryl, —ORa, —N(Ra)2, —SRa, —CN, —SCN, —C(═NRa)Ra, —C(═NRa)ORa, —C(═NRa)N(Ra)2, —C(═O)Ra, —C(═O)ORa, —C(═O)N(Ra)2, —NO2, —NRaC(═O)Ra, —NRaC(═O)ORa, —NRaC(═O)N(Ra)2, —OC(═O)Ra, —OC(═O)ORa, or —OC(═O)N(Ra)2;
• each instance of Ra is independently hydrogen, substituted or unsubstituted, C1-6 alkyl, substituted or unsubstituted, C2-6 alkenyl, substituted or unsubstituted, C2-6 alkynyl, substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl, substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl, substituted or unsubstituted phenyl, substituted or unsubstituted, 5- or 6-membered, monocyclic heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or a nitrogen protecting group when attached to a nitrogen atom;
• or two instances of Ra attached to the same nitrogen atom are joined to form substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl, or substituted or unsubstituted, 5- or 6-membered, monocyclic heteroaryl;
• each instance of T is independently a single bond, substituted or unsubstituted, C1-20 alkylene, substituted or unsubstituted, C2-20 alkenylene, substituted or unsubstituted, C2-20 alkynylene, substituted or unsubstituted, C2-20 heteroalkylene, substituted or unsubstituted, C2-20 heteroalkenylene, or substituted or unsubstituted, C2-20 heteroalkynylene, wherein:
• optionally one or more carbons in each instance of the substituted or unsubstituted, C1-20 alkylene, substituted or unsubstituted, C2-20 alkenylene, substituted or unsubstituted, C2-20 alkynylene, substituted or unsubstituted, C2-20 heteroalkylene, substituted or unsubstituted, C2-20 heteroalkenylene, and substituted or unsubstituted, C2-20 heteroalkynylene are independently replaced with substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• and
• optionally one or more heteroatoms in each instance of the substituted or unsubstituted, C2-20 heteroalkylene, substituted or unsubstituted, C2-20 heteroalkenylene, and substituted or unsubstituted, C2-20 heteroalkynylene are independently replaced with substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• each instance of RB is independently hydrogen, halogen, or substituted or unsubstituted, C1-6 alkyl;
• each instance of b is independently an integer from 1 to 20, inclusive;
• e is an integer from 1 to 10, inclusive;
• and
• X is —ORC or —N(RD)2, wherein:
• RC is hydrogen, substituted or unsubstituted, C1-1000 alkyl, substituted or unsubstituted, C2-1000 alkenyl, substituted or unsubstituted, C2-1000 alkynyl, substituted or unsubstituted, C1-1000 heteroalkyl, substituted or unsubstituted, C2-1000 heteroalkenyl, substituted or unsubstituted, C2-1000 heteroalkynyl, an oxygen protecting group, or a leaving group;
• and
• each instance of RD is independently hydrogen, substituted or unsubstituted, C1-1000 alkyl, substituted or unsubstituted, C2-1000 alkenyl, substituted or unsubstituted, C2-1000 alkynyl, substituted or unsubstituted, C1-1000 heteroalkyl, substituted or unsubstituted, C2-1000 heteroalkenyl, substituted or unsubstituted, C2-1000 heteroalkynyl, or a nitrogen protecting group.